title: N0539 phase II trial of fulvestrant and bevacizumab in patients with metastatic breast cancer previously treated with an aromatase inhibitor: a North Central Cancer Treatment Group (now Alliance) trial.
abstract: BACKGROUND
  Based on preclinical studies, the vascular endothelial pathway is an important mechanism for estrogen receptor resistance. We conducted a phase II study of fulvestrant and bevacizumab in patients with aromatase inhibitor pretreated metastatic breast cancer.
  
  
  METHODS
  A single-stage phase II study was conducted with these objectives: 6-month progression-free survival (PFS), tumor response, toxic effect, and overall survival. Regimen: 250 mg fulvestrant days 1 and 15 (cycle 1) then day 1 (cycle 2 and beyond) and 10 mg/kg bevacizumab days 1 and 15 of each 4-week cycle.
  
  
  RESULTS
  At interim analysis, 20 eligible patients initiated treatment, 11 were progression free and on treatment at 3 months, not meeting the protocol-specified efficacy requirements (at least 12 of 20). Accrual remained open during interim analysis with 36 patients enrolling before final study closure. Among the 33 eligible patients, the median PFS was 6.2 months [95% confidence interval (CI) 3.6-10.1 months]. Of the 18 with measurable disease, 4 (22%) patients (95% CI 6% to 48%) had a confirmed tumor response (1 complete, 3 partial). The most common grade 3/4 adverse events were hypertension 3 (9%) and headache 3 (9%).
  
  
  CONCLUSIONS
  The fulvestrant/bevacizumab combination is safe and tolerable; however, it did not meet its statistical end point.
authors.affiliation: Division of Hematology/Oncology, Mayo Clinic, Jacksonville.
authors.forename: W W
authors.initials: WW
authors.lastname: Tan
authors.affiliation: Section of Biostatistics, Mayo Clinic, Scottsdale.
authors.forename: A C
authors.initials: AC
authors.lastname: Dueck
authors.affiliation: Metro Minnesota CCOP, St Louis Park.
authors.forename: P
authors.initials: P
authors.lastname: Flynn
authors.affiliation: Sanford Medical Center, Fargo.
authors.forename: P
authors.initials: P
authors.lastname: Steen
authors.affiliation: Metro Minnesota CCOP, St Louis Park.
authors.forename: D
authors.initials: D
authors.lastname: Anderson
authors.affiliation: Carle Cancer Center, Urbana.
authors.forename: K
authors.initials: K
authors.lastname: Rowland
authors.affiliation: Divison of Hematology/Oncology, Mayo Clinic, Scottsdale, USA.
authors.forename: D
authors.initials: D
authors.lastname: Northfelt
authors.affiliation: Division of Hematology/Oncology, Mayo Clinic, Jacksonville. Electronic address: perez.edith@mayo.edu.
authors.forename: E A
authors.initials: EA
authors.lastname: Perez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004958:Estradiol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011788:Quality of Life; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D011960:Receptors, Estrogen; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077267:Fulvestrant; D000068258:Bevacizumab; D004958:Estradiol
keywords: antiangiogenesis agent; aromatase inhibitor resistance; bevacizumab; estrogen receptor antagonist; fulvestrant; metastatic breast cancer